Abstract Stem cell lineage determination is governed not only by biochemical cues but also by the organization and force-generating state of the cytoskeleton, which integrates extracellular mechanical cues into transcriptional and epigenetic responses. Cytoskeletal organization and remodeling play essential roles in stem cell fate determination, as well as other relevant biological processes including development, tissue regeneration, and disease progression. In this review, we first outline the different types of cytoskeletal structures—actin filaments, microtubules, and intermediate filaments—and their coordinated roles in cell shape, polarity, and contractility. We then discuss how extracellular cues, including matrix stiffness, geometry, topography, shear, stretch, and compression remodel cytoskeletal distribution and adhesion dynamics to affect stem cell lineage commitment. We highlight matrix viscoelasticity and stress relaxation as time-dependent mechanical regulators that modulate traction transmission, focal adhesion, and cytoskeletal tension, thereby directing stem cell differentiation outcomes beyond stiffness alone. We next discuss mechanotransduction pathways, such as RhoA/ROCK-mediated contractility, Wnt/β-catenin, Piezo1/Piezo2, and YAP/TAZ nuclear shuttling, which couple cytoskeletal forces to gene regulation. We further summarize quantitative approaches to measure cell molecular forces, including traction force microscopy, molecular tension sensors, and advanced live-cell imaging platforms. Finally, we discuss the translational potential of cytoskeleton-informed design principles in regenerative medicine, where they can be leveraged to improve stem cell biomanufacturing, optimize tunable biomaterials, and develop more predictive mechanopathology models. Together, these developments will establish cytoskeletal organization as a controllable, engineerable lever for directing stem cell fate and enabling functional tissue formation.
Abstract Regulatory T-cells (Tregs) hold significant promise for the treatment of autoimmune diseases and transplant rejection, yet their clinical translation is limited by inefficient and inconsistent manufacturing strategies that fail to generate stable and functional cell populations at scale. Current ex vivo expansion approaches rely on bead-based activation systems that often induce transient FOXP3 expression and variable product quality. Here, we present a bioinspired hydrogel-based activation platform that enables robust expansion and stabilization of regulatory T-cell phenotypes from primary human T-cells. Using PEG-based hydrogels functionalized with anti-CD3 and anti-CD28, we demonstrate significantly enhanced induction and persistence of FOXP3+ T-cells compared to industry-standard bead-based activation. Hydrogel activation yields >50% FOXP3+ cells and supports sustained expression following removal of activation cues, in contrast to the transient regulatory phenotype observed with conventional methods. Importantly, hydrogel-activated cultures exhibit substantial expansion of both CD4+ and CD8+ FOXP3+ populations, alongside increased expression of key immunosuppressive cytokines including IL-10 and TGF-β. While coculture with M2-polarized macrophages modestly enriches regulatory phenotypes, it reduces overall cell expansion and provides limited benefit beyond hydrogel activation alone. These findings identify material-mediated activation as a dominant driver of Treg differentiation and stability. Together, this work establishes a scalable, biomaterial-based strategy for generating high-quality regulatory T-cell products and provides a foundation for improving the manufacturing of Treg-based therapies.
Traditional Chinese medicine (TCM) compound formulas are widely employed in the clinical management of osteoporosis; however, their principal bioactive constituents and primary molecular targets remain poorly characterized. Consequently, there is an urgent need for systematic functional exploration of TCM-derived chemicals. In this study, we applied a network pharmacology-based approach to screen four canonical TCM compound prescriptions for antiosteoporotic compounds, identifying a total of 20 candidate molecules. Among these, quercetin was selected as a lead compound for the synthesis of biologically active carbon dots (CDs), which were then integrated with mesoporous silica nanoparticles (MSNs) to construct a reactive oxygen species (ROS)-responsive nanocarrier system. In vitro cellular assays demonstrated that both the quercetin-derived CDs and the drug-loaded nanocarriers exhibited excellent cytocompatibility, robust osteogenic-promoting activity, and potent osteoclast-inhibitory effects. Collectively, our findings underscore the utility of network pharmacology in identifying quercetin as a promising TCM-derived lead compound for osteoporosis intervention, and the rational functionalization strategy developed herein provides a valuable paradigm for advancing the therapeutic application of TCM-derived chemicals in bone metabolic disorders.
Abstract With the advancement of micro/nanomotors toward greater functionalization and intelligence, increasing attention has been devoted to their biomedical applications, which in turn impose more stringent requirements on biocompatibility and propulsion performance. Given that glucose serves as both an energy source and a metabolic intermediate in living cells, glucose-fueled micro/nanomotors hold particular promise for life science applications. In this review, we focus on glucose-fueled micro/nanomotors driven by cascade catalytic reactions, which exhibit inherently favorable biocompatibility and enhanced propulsion. Beginning with the fundamental principles of cascade reactions, we summarize the types and current development status of cascade reactions employing glucose as a substrate. We then discuss the design strategies of glucose-fueled cascade catalytic micro/nanomotors in terms of carrier engineering, enzyme loading methodologies, propulsion mechanisms, and motility behaviors. Subsequently, we review recent progress in biomedical applications, with particular emphasis on in vitro and in vivo studies for cancer therapy, biological barrier penetration, and antibiofilm eradication. Finally, we conclude by addressing the current limitations of glucose-fueled cascade catalytic micro/nanomotors and the challenges that must be overcome to advance their practical translation.
Abstract Drug-loaded coatings significantly improve the bioactivities of multiple medical devices. The most widespread applications are assembling anticoagulant coatings on blood-contacting medical devices to enhance blood compatibility and applying antibacterial coatings to prevent device-induced infection. Notably, a vicious cycle between bacterial infection and thrombosis may result in deterioration of condition and even lead to treatment failure. Thrombosis caused by blood incompatibility of medical devices provides niduses for bacterial colonization, whereas bacterial endotoxins accelerate thrombosis by activating platelets. In some situations, the interactional process can also trigger inflammatory responses and calcification processes. Therefore, the demands for anticoagulant and antibacterial are necessary and mutually influenced. This review presents a summary of current commercial drug-loaded anticoagulant coatings and a detailed report on novel drug-loaded coatings with anticoagulant and/or antibacterial effects. We highlight the synthesis and assembly techniques, drug-release duration, and biofunctional behavior of referenced coatings. Based on careful comparison and comprehensive summary of the state-of-the-art literature, this review reveals the difficulties in large-scale production of the emerging coatings and the functional differences compared to the existing commercial coatings, and predicts the general process for manufacturing and commercialization.
